Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cAMP-dependent protein kinases comprise two enzyme forms designated as type I and type II. The type II enzyme can catalyze an autophosphorylation reaction whereby phosphate is transferred from ATP to one seryl residue on each regulatory subunit monomer. Since this reaction can occur in the absence of cAMP-induced enzyme dissociation, it has been used as a probe to identify one site of interaction between the catalytic subunit (C) and the type II regulatory subunit (R11). The type I cAMP-dependent protein kinase does not catalyze an analogous reaction; however, if cGMP-dependent protein kinase is substituted for C, the type I regulatory subunit (R1) becomes phosphorylated. The effects of cyclic nucleotides on this reaction, coupled with the ability of R1 to serve as an inhibitor of cGMP-dependent protein kinase suggest that this phosphorylation also occurs within an important functional domain on R1. A comparison of the autophosphorylation site on R11 with the cGMP-dependent protein kinase catalyzed phosphorylation site on R1 indicates that each modification takes place within a similar proteolytically sensitive region. On each subunit, this sensitive "hinge" region lies distal to the functional domain responsible for regulatory subunit dimerization and proximal to that responsible for cAMP binding. Phosphorylation of the "hinge" region decreases the affinity of each regulatory subunit for C, although the magnitude of this change appears greater for R1 than for R11. Phosphorylation of R1 also reduces the stoichiometry of cAMP binding from two to one mole of cAMP bound per mole of R1 monomer. These results suggest that the "hinge" regions of both R1 and R11 form part of the interaction site between the regulatory subunit and C; and, in the case of R1, it also forms a portion of one of two cAMP-binding sites. The amino acid sequence surrounding the phosphorylated serine of each regulatory subunit has been determined: R11: D-R-R-V-S(P)-V R1: R-R-R-R-G-A-I-S(P)-A It is thought that the number and position of the basic amino acid residues proximal to the modified serine may be responsible, in part, for determining the susceptibility of each site to phosphorylation by cAMP or cGMP-dependent protein kinase. Both R1 and R11 exist as phosphoproteins in vivo. Dephosphorylation of purified "native" phospho-R1 is without effect on the ability of R1 to interact with either C or cAMP. The site phosphorylated in vivo is therefore distinct from that modified in vitro by cGMP-dependent protein kinase. In addition to the autophosphorylation site, R11 possesses a second, less enzymatically reactive, phosphorylation site that is modified in vivo. Dephosphorylation of this site is also without apparent effect on the functional properties of R11. The kinases responsible for catalyzing the phosphorylation of R1 and the cryptic site on R11 and the role that these modifications play in modulating kinase activity are currently unknown but are under active investigation.
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PMID:Phosphorylation of cAMP-dependent protein kinase subunits. 628 16

Drastic changes in the environment during a lifetime require developmental and physiological flexibility to ensure animal survival. Desert locusts, Schistocerca gregaria, live in an extremely changeable environment, which alternates between periods of rainfall and abundant food and periods of drought and starvation. In order to survive, locusts display an extreme form of phenotypic plasticity that allows them to rapidly cope with these changing conditions by converting from a cryptic solitarious phase to a swarming, voracious gregarious phase. To accomplish this, locusts possess different conserved mediators of phenotypic plasticity. Recently, attention has been drawn to the possible roles of protein kinases in this process. In addition to cyclic AMP-dependent protein kinase (PKA), also cyclic GMP-dependent protein kinase (PKG), which was shown to be involved in changes of food-related behavior in a variety of insects, has been associated with locust phenotypic plasticity. In this article, we study the transcript levels of the S. gregaria orthologue of the foraging gene that encodes a PKG in different food-related, developmental and crowding conditions. Transcript levels of the S. gregaria foraging orthologue are highest in different parts of the gut and differ between isolated and crowd-reared locusts. They change when the availability of food is altered, display a distinct pattern with higher levels after a moult and decrease with age during postembryonic development.
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PMID:Developmental- and food-dependent foraging transcript levels in the desert locust. 2395 60

The contractile function of striated muscle cells is altered by oxidative/nitrosative stress, which can be observed under physiological conditions but also in diseases like heart failure or muscular dystrophy. Oxidative stress causes oxidative modifications of myofilament proteins and can impair myocyte contractility. Recent evidence also suggests an important effect of oxidative stress on muscle elasticity and passive stiffness via modifications of the giant protein titin. In this review we provide a short overview of known oxidative modifications in thin and thick filament proteins and then discuss in more detail those oxidative stress-related modifications altering titin stiffness directly or indirectly. Direct modifications of titin include reversible disulfide bonding within the cardiac-specific N2-Bus domain, which increases titin stiffness, and reversible S-glutathionylation of cryptic cysteines in immunoglobulin-like domains, which only takes place after the domains have unfolded and which reduces titin stiffness in cardiac and skeletal muscle. Indirect effects of oxidative stress on titin can occur via reversible modifications of protein kinase signalling pathways (especially the NO-cGMP-PKG axis), which alter the phosphorylation level of certain disordered titin domains and thereby modulate titin stiffness. Oxidative stress also activates proteases such as matrix-metalloproteinase-2 and (indirectly via increasing the intracellular calcium level) calpain-1, both of which cleave titin to irreversibly reduce titin-based stiffness. Although some of these mechanisms require confirmation in the in vivo setting, there is evidence that oxidative stress-related modifications of titin are relevant in the context of biomarker design and represent potential targets for therapeutic intervention in some forms of muscle and heart disease.
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PMID:Emerging importance of oxidative stress in regulating striated muscle elasticity. 2537 78